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Copper metabolism in Acanthamoeba castellanii
Doležalová, Taťána ; Šuťák, Róbert (advisor) ; Mladěnka, Přemysl (referee)
Copper is an essential element that, due to its redox properties, is involved as a cofactor in many enzymes, the most well-known example is the cytochrome c oxidase. At the same time, in higher concentrations, this element shows toxic effects on several levels, it can disrupt iron-sulfur clusters, damage proteins and lead to cell death. This is the reason why this thesis studies copper metabolism in the parasitic amoeba Acanthamoeba castellanii, which causes serious diseases such as acanthamoeba keratitis or granulomatous amoebic encephalitis. Understanding how copper homeostasis is maintained in this organism could lead to targeted disruption of this balance and the exploitation of the toxic effects of copper. In this work, the function of the P-type ATPase homologous to CCC2 from Saccharomyces cerevisiae, responsible for the transfer of copper ions from the cytoplasm to the Golgi apparatus, was characterized by functional complementation. Furthermore, a carrier from the Ctr family has been described that transfers copper ions presumably across the cytoplasmic membrane. The expression of these carriers was monitored in copper excess and deficiency. To get a better picture of how A. castellanii maintains copper homeostasis, the cellular accumulation of copper and the ability of this amoeba to deal...
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Copper metabolism in pathogenic eukaryotic microorganisms
Doležalová, Taťána ; Šuťák, Róbert (advisor) ; Pilátová, Jana (referee)
Copper is an essential trace element for almost every living organism. Its fundamental role in metabolism is caused by the redox properties of this metal. Owing to that it is a vital cofactor of many enzymes participating in cell energy metabolism as well as in the detoxification of reactive oxygen species. Nevertheless, too high copper concentration can damage the cells. The toxic effect of copper is manifested usually as the production of hydroxyl radicals distorting the cell structures. It can also damage Fe-S clusters that are essential for many enzymes. To avoid toxic manifestations the cell must balance on the edge of proper copper import and regulated export. Many specialized transporters and ATPases serve exclusively for copper transport. There are also known metallochaperones binding the potentially toxic metals and transporting them to the target protein. An interesting role in metabolism is played by the metallothioneins that bind cytosolic copper. Understanding copper homeostasis in pathogenic organisms reveals many interesting possibilities for better targeted treatment. For example, diseases caused by opportunistic fungi like Candida albicans, Aspergillus fumigatus or Cryptococcus neoformans contribute significantly to the deaths of immunodeficient patients. Some copper metabolism...
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